Glycosignals in Cancer: Mechanisms of Malignant Phenotypes by Koichi Furukawa & Minoru Fukuda

Author:Koichi Furukawa & Minoru Fukuda
Language: eng
Format: epub
Publisher: Springer Japan, Tokyo

To define the molecular mechanism underlying αGlcNAc antimicrobial activity, we focused in particular on morphological changes seen in H. pylori cultured in the presence of αGlcNAc (Fig. 7.2c) (Kawakubo et al. 2004). We noted that those changes were similar to those seen in H. pylori cultured in the presence of β-lactamase inhibitors (Enroth et al. 1999). Thus, we speculated that treatment with αGlcNAc had an effect on the H. pylori cell wall. Hirai et al. (1995) previously demonstrated that the H. pylori cell wall contains a unique glycolipid, cholesteryl-α-D-glucopyranoside (CGL), as well as its derivatives. CGL biosynthesis is catalyzed by cholesterol α-glucosyltransferase (αCgT), which transfers glucose (Glc) from UDP-Glc to cholesterol with an α1,3-linkage. Molecular mimicking between α1,4-linked GlcNAc in gland mucin and α1,3-linked Glc in CGL suggested that αGlcNAc suppressed αCgT enzymatic activity by an end-product inhibitory mechanism. Thus, we analyzed glycolipid fractions isolated from H. pylori cultured in the presence of αGlcNAc (+) or αGlcNAc (−) using mass spectrometry (Kawakubo et al. 2004). We found that CGL levels in H. pylori cultured with αGlcNAc (+) were significantly lower than those seen in H. pylori cultured with αGlcNAc (−), suggesting that αGlcNAc directly inhibits CGL biosynthesis by H. pylori in vivo. Subsequently, we used expression cloning to isolate αCgT gene from H. pylori (Lee et al. 2006) and proved that αCgT enzymatic activity is inhibited by core2-branched O-glycans displaying αGlcNAc in vitro (Lee et al. 2008). We also showed that an active form of αCgT is present in the H. pylori membrane fraction, suggesting that bacterial αCgT is likely accessible to αGlcNAc in gland mucin (Hoshino et al. 2011).

Download

Copyright Disclaimer:
This site does not store any files on its server. We only index and link to content provided by other sites. Please contact the content providers to delete copyright contents if any and email us, we'll remove relevant links or contents immediately.